Enzymes inhibition profiles and antibacterial activities of benzylidenemalononitrile derivatives

GÜLLER P., Dağalan Z., Güller U., Çalışır U., NİŞANCI B.

Journal of Molecular Structure, cilt.1239, 2021 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1239
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.molstruc.2021.130498
  • Dergi Adı: Journal of Molecular Structure
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, INSPEC
  • Anahtar Kelimeler: Acetylcholinesterase, Antibacterial, Carbonic anhydrase, Molecular docking, Structure-activity relationship (SAR), CARBONIC-ANHYDRASE INHIBITORS, ALZHEIMERS-DISEASE, IN-SILICO, ANTIMICROBIAL ACTIVITY, ANTIOXIDANT ACTIVITY, ISOFORMS I, ACETYLCHOLINESTERASE, VITRO, CHEMISTRY, DESIGN
  • Atatürk Üniversitesi Adresli: Evet

Özet

© 2021 Elsevier B.V.The activities of enzymes can be targeted in the treatment of some diseases. Recently, this strategy has been used frequently in the development of new drugs. Carbonic anhydrase isozymes (CA-I and CA-II) and acetylcholine esterase (AChE) are some of these enzymes. So, in the present study, we aimed to investigate primer effects of presynthesized benzylidenemalononitrile derivatives (1-11) on the enzymes via in vitro inhibition study, to clarify inhibition profiles of derivatives through molecular docking, and to examine their effects against some bacterial strains. For this purpose, firstly the benzylidenemalononitrile derivatives were synthesized starting from readily available aldehydes and malononitrile with catalyst free conditions in aqueous medium just in 15 minutes (11 examples). Then, biochemical and molecular docking studies were performed. CA-I, CA-II and AChE was isolated from the human erythrocyte and the inhibition effects of synthesized derivatives were examined through both in vitro and in silico approaches. While compound 5 was found as the most effective inhibitor on hCA-I and hCA-II with Ki constant of 7.51±2.25 and 11.92±2.22 µM respectively, it was determined that compound 3 showed the highest inhibition effect on hAChE with Ki of 0.058±0.014 µM. From the antibacterial studies, it was found that while molecule 5 is the most effective compound against K. pneumonia molecule 7 is the most effective compound against S. aureus.